TW200838496A - Agent for alleviating or preventing stress symptoms and agent for improving mental conditions - Google Patents
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- TW200838496A TW200838496A TW096143542A TW96143542A TW200838496A TW 200838496 A TW200838496 A TW 200838496A TW 096143542 A TW096143542 A TW 096143542A TW 96143542 A TW96143542 A TW 96143542A TW 200838496 A TW200838496 A TW 200838496A
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- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 1
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- 229940113147 shellac Drugs 0.000 description 1
- 235000015170 shellfish Nutrition 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 235000012046 side dish Nutrition 0.000 description 1
- 230000037321 sleepiness Effects 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 229940048086 sodium pyrophosphate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
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- 239000008117 stearic acid Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 239000009396 suanzaoren Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 235000020238 sunflower seed Nutrition 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000003760 tallow Substances 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- 235000007586 terpenes Nutrition 0.000 description 1
- 235000019818 tetrasodium diphosphate Nutrition 0.000 description 1
- 239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 108060008226 thioredoxin Proteins 0.000 description 1
- 229940094937 thioredoxin Drugs 0.000 description 1
- 238000012034 trail making test Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- GWBUNZLLLLDXMD-UHFFFAOYSA-H tricopper;dicarbonate;dihydroxide Chemical compound [OH-].[OH-].[Cu+2].[Cu+2].[Cu+2].[O-]C([O-])=O.[O-]C([O-])=O GWBUNZLLLLDXMD-UHFFFAOYSA-H 0.000 description 1
- 235000001019 trigonella foenum-graecum Nutrition 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 150000003700 vitamin C derivatives Chemical class 0.000 description 1
- 150000003712 vitamin E derivatives Chemical class 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 235000020234 walnut Nutrition 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 230000002087 whitening effect Effects 0.000 description 1
- 239000008434 yi-zhi Substances 0.000 description 1
- 239000010017 yuan zhi Substances 0.000 description 1
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/111—Aromatic compounds
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/105—Aliphatic or alicyclic compounds
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/075—Ethers or acetals
- A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
- A61K31/09—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
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- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Food Science & Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
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- Diabetes (AREA)
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Abstract
Description
200838496 九、發明說明: 【發明所屬之技術領域】 本發明係關於一種壓力症狀舒緩劑及其預防劑、以及精 神狀況改善劑。詳細而言,本發明提供一種由於曰常或非 曰常狀況下產生的精神壓力所導致之緊張等壓力症狀之舒 緩劑或其預防劑、以及改善希望改善的精神狀況之精神狀 況改善劑。 【先前技術】 〜人們在日常生活中承受各種精神壓力,會不知不覺中變 2緊張起來。如今人們普遍認識到精神壓力的積累有時亦 會導致嚴重的疾病,避免屢力或者舒緩及減輕屢力在曰常 生活中成為重要的事項。作為必須由醫生進行治療之症 狀’已知有強迫神經症、自主神經失調症等,對該等疾病 正分別考慮採取其治療法,但尚不理想。除此之外,現狀 為對於無須進行治療的較輕程度,例如極輕的緊張症或於 2等時易緊張而無法充分發揮實力而始終焦躁情緒不佳 、-般常見的狀態,甚至連相應之處理方法都不明確。 細例如,作為由於精神壓力而導致之症狀,則有緊張、神 :過敏症、上火、失眠、焦躁感、抽摘、口吃、精神疲勞 :二胃腸障礙、胃痛、脫毛症、恐怖感、無力感、虛弱感、 Ζ不振、頭痛、口渴等其他視各人而不同之各種症狀。 :面,顯然與精㈣力無關,但於曰常生活中的精神 r 存在易怒、無熱情、憂鬱、缺乏幸福感、缺乏自 …、乏自我存在意識、擔心、缺乏集中力、過慮、生存 126845.doc 200838496 意義降低、不高興、消沉等一般希望加以改善之各 狀況。 Τ 辅酶Q,根據其側鏈之重複結構已知有輔酶qi至輔酶 Q13,但哺乳動物的主要輔酶㈣辅酶⑽,人類使用辅酶 Qi〇。輔酶Q1G存在於粒線體、溶酶體、冑爾基體'微粒體、 過氧化體(P⑽xis〇me)、或細胞膜等中,作為電子傳遞系统 之構成成分,係維持與ATP產生活化、生物體内的抗氧化 作用、膜穩定化有關之生物體機能必不可少的物質。 辅酶⑽中已知有氧化型與還原型,將氧化型命名為泛 酿’將還原型命名為泛醇。已知有,於電子傳遞系統中辅 酶Q係藉由反覆進行氧化還原而傳遞電子。又,僅還原型顯 示有抗氧化活性,生物體内夕鮭給^ 聪円之辅酶Q的較多部分係以還原型 而存在’因而認為還原型為主要的形態。然而,還原型辅 酶Q在氧化穩定性方面有問題 Π碭因而目刖為止,產業上僅使 用氧化型輔酶Q。根據如此背景, 月厅、於6己載為辅酶Q之情形 時,一般而言只要無特別言贷明目t ± # 、 〜况月則表不乳化型輔酶Q,於指明 為還原型之情形時,則記載為、、多_ 戟局,乏知或者逛原型辅酶Q。 氧化型輔酶Q10先前一直传用你燃 里你用作鬱血性心衰竭之辅助 藥,但近年來作為補充品而在入 阳在全世界被廣泛使用。其生理 活性被廣泛研究,已知有抗棰民严 ^ ^ ’、 ,柷糖尿病、抗疲勞、抗動脈硬化 等許多生理活性(專利文獻。 3)作為辅S#Q10之抗壓力作 用,報告有將氧化型辅酶Ql〇盘一 νιυ興一十八醇或者刺五加併用 時,對寒冷應激反應有用(真法丨 5用(寻利文獻4、5),但該等係對物理 性寒冷的應激之應答,而對於Μ= a 了於補酶Q對通常生活中所產生的 126845.doc 200838496 精神壓力之效果卻全然不知。 [專利文獻1 ]日本專利特開平7 - 3 3 0 5 8 4 [專利文獻2]日本專利特開平7-330593 [專利文獻3]曰本專利特開平i〇-28756〇 [專利文獻4]曰本專利特開2〇〇4-292355 [專利文獻5]日本專利特開2〇〇4·2ΐ〇728 【發明内容】 [發明所欲解決之問題]200838496 IX. Description of the Invention: [Technical Field] The present invention relates to a stress symptom soothing agent and a prophylactic agent thereof, and a mental condition improving agent. In particular, the present invention provides a stressor or a prophylactic agent thereof for stress symptoms such as stress caused by stress caused by abnormal or abnormal conditions, and a psychoticity improving agent for improving a mental condition which is desired to be improved. [Prior Art] ~ People withstand various mental stresses in their daily lives, and they will become unconscious. It is now widely recognized that the accumulation of mental stress can sometimes lead to serious illnesses, avoiding repeated efforts or soothing and alleviating the importance of repeated efforts in everyday life. As a symptom that must be treated by a doctor, there are known obsessive-compulsive disorder, autonomic dysfunction, etc., and the treatment is considered separately for these diseases, but it is not satisfactory. In addition, the status quo is a relatively mild degree of no need for treatment, such as extremely light stress disorder or difficulty in exerting strength when 2 is not strong enough, and always has a bad mood, a common state, and even corresponding The treatment methods are not clear. Fine, for example, as a result of mental stress, there are tension, God: allergies, getting angry, insomnia, irritability, extraction, stuttering, mental fatigue: two gastrointestinal disorders, stomach pain, hair loss, horror, weakness Feelings, feelings of weakness, lack of energy, headache, thirst, and other symptoms that vary from person to person. : Face, obviously has nothing to do with the essence (four) force, but the spirit of life in the constant life is irritating, no enthusiasm, melancholy, lack of happiness, lack of self..., lack of self-presence, worry, lack of concentration, care, survival 126845.doc 200838496 The conditions that are generally expected to be improved, such as reduced meaning, unhappiness, depression, etc.辅 Coenzyme Q, known as coenzyme qi to coenzyme Q13 according to the repeat structure of its side chain, but the main coenzyme of the mammal (4) coenzyme (10), human coenzyme Qi〇. Coenzyme Q1G is present in mitochondria, lysosomes, steroidal microsomes, peroxisomes (P(10)xis〇me), or cell membranes, and is a component of an electron transport system that maintains activation with ATP, organisms. It is an essential substance for the anti-oxidation action and the function of the organism related to membrane stabilization. An oxidized form and a reduced form are known in the coenzyme (10), and the oxidized form is named as a brewer. The reduced form is named panthenol. It is known that in the electron transport system, the coenzyme Q system transfers electrons by repeatedly performing redox. Further, only the reduced form shows an antioxidant activity, and a large part of the coenzyme Q in the body of the living body is present in a reduced form, and thus the reduced form is considered to be the main form. However, the reduced coenzyme Q has problems in oxidative stability. Therefore, only the oxidized coenzyme Q has been used in the industry. According to this background, when the moon hall and 6 are contained as coenzyme Q, generally, as long as there is no special credit, t ± #, and the condition is not emulsified coenzyme Q, which is indicated as a reduced type. At the time, it is recorded as, more than _ 戟 ,, lack of knowledge or visit prototype coenzyme Q. Oxidized coenzyme Q10 has been used in your previous use as an adjunct to your septic heart failure, but it has been widely used in the world as a supplement in recent years. Its physiological activity has been extensively studied, and many physiological activities such as anti-Ministry, anti-fatigue, anti-fatigue, and anti-arteriosclerosis have been known (Patent Literature. 3) as an anti-stress effect of the auxiliary S#Q10. When oxidized coenzyme Ql 〇 一 ν υ υ υ 或者 或者 或者 or acanthopanax senticosus, it is useful for cold stress response (true method 丨 5 (search for literature 4, 5), but these are cold physical The response of stress, but the effect of 补 = a on the 126845.doc 200838496 mental stress produced in normal life is completely unknown. [Patent Document 1] Japanese Patent Laid-Open No. 7 - 3 3 0 5 [Patent Document 2] Japanese Patent Laid-Open No. Hei 7-330593 [Patent Document 3] Japanese Patent Laid-Open Publication No. Hei-28756 [Patent Document 4] Japanese Patent Laid-Open No. 2〇〇4·2ΐ〇728 [Summary of the Invention] [Problems to be Solved by the Invention]
本發明之目的在於提供一種作為食品、健康食品、營養 辅助食品、補充品、藥品、帛藥品、寵物食品、或飼料而 有用的壓力症狀舒緩劑或預防劑或者精神狀況改善劑,以 及含有其之組合物。 [解決問題之技術手段] 本發明者們鑒於上述情況淮/ ^ #丄 月,兄進仃了努力研究,結果發現辅 酶Q具有舒緩、預防由於緊張辇 糸張等精神壓力而引起之症狀、而 且改善精神狀況之優異作用 ^ 攸而最終完成本發明。即, tr月係關於-種壓力症狀舒緩劑或預_或者精神狀況 以,該壓力症狀舒緩劑或預防劑或者精神狀 錢善劑之食品、健康食品、營養辅助食品、補充品、藥 口口、準藥品、寵物食品或飼料· >v 劑或者精神狀況改善#丨之特心A ml預防 特铽在於··將氧化型辅酶Q及/或 通原型辅酶Q作為有效成分。 一 即,本發明提供如以下者: [1 ]種虔力症狀舒緩或預防_ ^ 人了只防劓,其特徵在於··將下述式(1) 126845.doc 200838496 酶 所表示之氧化型辅酶Q及/或下述式(2)所表示之還原型補 Q作為有效成分。 [化1] 〇An object of the present invention is to provide a stress symptom soothing agent or a preventive agent or a mental condition improving agent which is useful as a food, a health food, a nutritional supplement food, a supplement, a medicine, a sputum medicine, a pet food, or a feed, and the same combination. [Technical means for solving the problem] In view of the above-mentioned situation, the inventors of the present invention have tried hard to study, and found that Coenzyme Q has the symptoms of soothing and preventing mental stress caused by stress and tension, and The excellent effect of improving the mental condition is finally completed. That is, tr month is a kind of stress symptom soothing agent or pre- or mental state, the stress symptom soothing agent or prophylactic agent or mental food agent food, health food, nutritional supplement food, supplement, medicine mouth , quasi-drugs, pet foods or feeds · > v agents or mental condition improvement #丨之特心 A ml prevention features —— oxidized coenzyme Q and / or prototype coenzyme Q as active ingredients. That is, the present invention provides the following: [1] The symptoms of sputum stress are relieved or prevented _ ^ The person is only sputum-proof, and is characterized by the oxidized form represented by the following formula (1) 126845.doc 200838496 enzyme The coenzyme Q and/or the reduced form Q represented by the following formula (2) are used as an active ingredient. [Chemical 1] 〇
[化2][Chemical 2]
(CH2CH=C(CH3)CH2)nH ⑴ 參(CH2CH=C(CH3)CH2)nH (1)
(CH2CH=C(CH3)CH2)nH h3co (2) (式中η表示1〜12之整數) [2] —種精神狀況改善劑,Α胜 J ,、特欲在於:將上述式(1)所主一 之氧化型輔酶Q及/或上述式〇 4表不 有效成分。 以(2)所表w㈣酶Q作為 辅酶Q為辅酶Ql〇(式中n [3] 如[1]或[2]所記載之藥劑,其中 為 10) 〇 [4] 如[1]至[3]中任一項所 — $所δ己載之藥劑,其中進一步含有營養 輔助成分及/或健康食品素材。 5養 [5] 如[4]所記載之劑,复 人^甲營養輔助成分為選自由胺基酸、 金屬離子、糖類、蛋白暂 、員、脂肪酸類、維生素類、維生 素Β衍生物、茶胺酸 ' h胺基丁酸(GABA)、曱肌肽 (anserine)、大豆胜肽、访 爪乳還原蛋白(thioredoxin)、小麥麩 126845.doc 200838496 貝水解物麵醯胺酸、乳肽、ω·3脂肪酸、鱗脂絲胺酸、還 原蝦紅素、多酚類、綠茶兒茶素、矣戒、銀杏葉萃取物、 聖約翰草(st. j〇Ws wort)、羅布麻萃取物、刺五加、山蔡 及木聚糖(lignan)類所組成之群中之工種以上。 [6] 如[4]所記載之藥劑’其中健康食品素材為選自由草藥 類、生藥類、簟類及該等之萃取物所組成之群中之傻以上。 [7] 如⑴至[6]中任-項所記载之劑,其中進—步含有抗氧化 物貝或/及抗氧化酶。(CH2CH=C(CH3)CH2)nH h3co (2) (where η represents an integer from 1 to 12) [2] A mental condition improving agent, Yu Sheng J, and the special desire lies in: (1) The oxidized coenzyme Q and/or the above formula 〇4 are not active ingredients. The (w) enzyme w (four) enzyme Q is used as coenzyme Q as coenzyme Ql (in the formula n [3] as described in [1] or [2], wherein 10) 〇 [4] such as [1] to [ 3] Any of the pharmacy contained in the δ, which further contains nutritional supplements and/or health food materials. 5养[5] The agent described in [4], the nutritional supplement component is selected from the group consisting of amino acids, metal ions, sugars, protein, workers, fatty acids, vitamins, vitamins and derivatives, tea Amino acid 'h-aminobutyric acid (GABA), anserine (aserine), soybean peptide, thioredoxin, wheat bran 126845.doc 200838496 shell hydrolysate proline, lactopeptide, ω· 3 fatty acids, serotonic acid, reduced astaxanthin, polyphenols, green tea catechins, medlar ring, ginkgo biloba extract, St. John's wort (st. j〇Ws wort), apocynum extract, thorn five More than the types of work in the group consisting of Jia, Shancai and lignan. [6] The agent described in [4] wherein the health food material is selected from the group consisting of herbs, crude drugs, terpenoids, and extracts thereof. [7] The agent according to any one of (1) to [6] wherein the step further comprises an antioxidant shellfish or/and an antioxidant enzyme.
m如m所記載之劑,其中抗氧化物質為選自由維生素^ 維生素_生物、維生素c、維生素❻生物、紅素、 維生素A、類胡蘿《素類、維生素B、維生素B衍生物:、類 黃剩類、還原煆紅素、㈣甘肽及㈣組成之群中之i種以 上0 [9]如[7]所記載之藥劑,其中抗氧化酶為選自由超氧化物歧 化酶(SOD ’ superoxide dismutase)、麵胱甘肽過氧化酶、麩 胱甘肽-S-轉移酶、麩胱甘肽還原酶、過氧化氫酶及抗壞血 酸過氧化酶所組成之群中之1種以上。 [1〇]-種食品、健康食品、營養辅助食品、補充品、寵物食 品或飼料’其含有如⑴至[9]中任—項所記載之藥劑。< [11]-種藥品或準藥品,其含有如[lm[9]中任—項所 之藥劑。 [12] —種壓力症狀舒緩或預防方法,其 有將有效量的上述 式(1)中所表示之氧化型辅酶Q及/或上述式(2)中所表二 還原型輔酶Q向投與對象投與之步驟。 厂、 126845.doc 200838496 =]—種精神狀況之改善方法,其係包含將有效量的上述式 (輔:表不之氧化型辅酶⑷或上述式⑺所表示之還原型 辅酶Q投與至投與對象者。 或[13]所記載之方法,其中輔酶㈣ 中 η為 1〇)。 乂 # 種里上述式⑴所表不之氧化型辅酶Q及/或上述式(2)所 二項型辅酶Q的用途,其係用以製造如[1]至[9]中任 營養辅助食品健康食品、 載之藥品或準藥品Γ物艮品或飼料,或者如[11]所記 如[15]所記载之用途,其中辅酶⑽輔酶⑽(式中打為 Π7] 一種商業包裝,苴句 型辅酶Q及^ ρ + "包3 .含有上述式(1)所表示的氧化 分之組合物:以及 =表示的還原型輔酶Q作為有效成 預防屢力症狀或者改盖二組合物可使用或應使用於舒緩或 次者改善精神狀況之記载物。 [發明之效果] 僅舒缓t f ^狀舒緩或預防劑或者精神狀況改善劑不 ;=Γ由於緊張等精神·力而導致之各種症狀,而 邊睡等^之㈣㈣之優異作用,並不伴發 曰睡·#田丨J作用,能夠進行日 症狀舒緩或預_ 之含有麼力 品、健康食。^ 劑之組合物,係以食 — μ 、相助食品、補充m、準荜品、 龍物食品、或飼料之形式丰^ 126845.doc 200838496 【實施方式】 以下痒細說明本發明。 本發明之壓力症狀舒 了 %或預防劑哎 (以下亦稱為本發明之南I彳 可積神狀況改善劑 徵在於··蔣 之氧化型辅酶Q及/或下诚 令下逑式(1)所表示 八(2)所表示之 有效成分。 〈還原型辅酶Q作為 [化1]m, as described in m, wherein the antioxidant is selected from the group consisting of vitamins, vitamins, vitamins, vitamins, vitamins, vitamins, vitamins, vitamins, vitamin B derivatives, The agent described in the group [9], wherein the antioxidant enzyme is selected from the group consisting of superoxide dismutase (SOD), wherein the antioxidant enzyme is selected from the group consisting of the super yellow dismutase (SOD). One or more of the group consisting of 'superoxide dismutase), glutathione peroxidase, glutathione-S-transferase, glutathione reductase, catalase, and ascorbate peroxidase. [1〇] - a food, a health food, a nutritional supplement, a supplement, a pet food or a feed. The medicament according to any one of (1) to [9]. < [11] A drug or quasi-drug containing the agent of [lm [9]. [12] A method for relieving or preventing stress symptoms, which comprises administering an effective amount of the oxidized coenzyme Q represented by the above formula (1) and/or the reduced coenzyme Q of the above formula (2) The steps taken by the object. Plant, 126845.doc 200838496 =] - a method for improving mental condition, comprising administering an effective amount of the above-mentioned formula (auxiliary: oxidized coenzyme (4) or reduced coenzyme Q represented by the above formula (7) to the cast Or the method described in [13], wherein η is 1〇 in the coenzyme (4).乂# The use of the oxidized coenzyme Q represented by the above formula (1) and/or the coenzyme Q of the above formula (2), which is used for the manufacture of the nutritional supplement foods of [1] to [9] Healthy food, drugs or quasi-drugs, or products or feeds, or as described in [11], [15], where coenzyme (10) coenzyme (10) (in the formula, Π7) a commercial package, 苴Sentence coenzyme Q and ^ ρ + " package 3. The composition containing the oxidized component represented by the above formula (1): and the reduced coenzyme Q represented by = as effective for preventing repeated symptoms or modifying the two compositions Use or should be used for the relief or the improvement of the mental condition of the second person. [Effect of the invention] Only the soothing or preventive agent or the mental condition improving agent is not relieved; Symptoms, while sleeping, etc. (4) (4), the excellent effect, not accompanied by sleepy · #田丨J action, can be used to relieve the symptoms of the day or pre- _ _ _ _ _ _ _ _ _ _ _ In the form of food-μ, help food, supplement m, quasi-荜, dragon food, or feed 126845.doc 200838496 [Embodiment] The present invention is described in detail below. The stress symptom of the present invention is % or the prophylactic agent 哎 (hereinafter also referred to as the South I 彳 神 状况 状况 状况 状况 本 蒋 蒋 蒋 蒋 蒋 蒋 蒋 蒋 蒋 蒋The oxidized coenzyme Q and/or the active ingredient represented by the eighth (2) represented by the formula (1). <Reduced Coenzyme Q as [Chemical 1]
00
CH3 (CH2CH-C(〇h )CHJ Η ° 2’ η [化2] (1) h3coh3coCH3 (CH2CH-C(〇h )CHJ Η ° 2' η [Chemical 2] (1) h3coh3co
OHΐέχ0"3 ^Y^(CH2CH=C(CH3)CH2)n Η OH η (2) 本發明之「壓力症狀 係指由於精神壓力所導致之各種 症狀,因此根據個人或者個體而不同,並無限定,具體可 舉出·緊張、神經過敏症、上火、失眠、易怒、憂鬱、焦 _感、抽搐、口吃、精神性疲勞感、胃腸障礙、胃痛、脫 毛、恐怖感、無力感、虛弱感、熱情降低、食慾不振、頭 痛、口渴、痙攣、皮膚乾燥等。本發明之壓力症狀舒緩或 預防劑具有舒缓上述壓力症狀或者預防此種症狀發生之作 用。 126845.doc -11 · 200838496 本發明之所謂壓力症狀之舒緩,係指使上述症狀自覺或 者不自覺地成為正常狀態(自覺或無他覺上述症狀之狀 態)、或者接近正常狀態。即,生活中,自覺上述症狀或者 由他人來看判斷為如此狀態之個體壓力症狀,可藉由攝取 (或者使其攝取)本發明之舒緩劑而自覺或者不自覺地改善 壓力症狀。 ϋ 又’本發明之所謂塵力症狀之預防,係指於特別狀況下, 例如預計考試之前或者在他人面前做什麼時等產生所謂虔 力的狀況之前’藉由日常攝取(或者使其攝取)本發明之預防 劑’可預防上述症狀之產生,或者降低產生頻率(即減輕壓 力症狀發病之危險)。 又,本發明之所謂精神狀況之改善,係指雖然明確與塵 力無關,但於日常生活中精神狀況中,使―般希望加以改 善之精神狀況向好的方向改善。至於上述希望改善之精神 狀況’可舉出:易怒、無熱情、憂鬱、缺乏幸福感、缺乏 自信、缺乏自我存在意識、擔心、缺乏集中力、過慮、活 力下降、不樂、消沉等精神狀況。 本發明之藥劑中所使用之氧化型輔酶Q,可利用先前眾所 周知t方法例㈣料、合成法、自動植物t萃取之方法 而獲得,但就安全性之觀點而言,較好的是利㈣酵法等 除合成法料之方法而獲得之全反式結構,例如可例示 K_ka·辅酶⑽(Kaneka股份有限公司註冊商標)。 對於獲得本發明之藥劑中所使用之還原型輔酶q之方 ,,並無特別限例如可㈣以先前方法獲得輔酶Q’然 126845.doc -12- 200838496 後利用層析法將流出液中的還原型辅酶Q部分加以濃縮之 方法等。於此情形時’視需要亦可於上述輔酶Q中添加硼氫 化鈉、二硫亞磺酸鈉(亞硫酸氫鈉)等一般的還原劑,利用常 法將上述輔酶Q中所含之氧化型辅酶Q還原成還原型辅酶 Q’然後利用層析法進行濃縮。又,亦可藉由使上述還原劑 作用於現有的高純度氧化型輔酶Q之方法而獲得。或者,亦 可使用含有還原型辅酶Q之菌體等。或者,亦可藉由將氧化 型輔酶Q與維生素類等具㈣原能力的物質—同製成製 劑’而於製劑中將氧化型輔酶Q還原成還原型辅酶。。又, 亦可較好地使用最近開始銷售之高純度還原型辅酶⑽即 kaNEKA QH(Kaneka股份有限公司註冊商標)。又,亦可直 t用利用公知的方法而獲得之作為氧化型與還原型的混 合物之辅酶Q。OHΐέχ0"3 ^Y^(CH2CH=C(CH3)CH2)n Η OH η (2) The "stress symptoms" of the present invention refer to various symptoms caused by mental stress, and therefore are not limited according to individuals or individuals. Specifically, stress, nervousness, getting angry, insomnia, irritability, depression, anxiety, convulsions, stuttering, mental fatigue, gastrointestinal disorders, stomach pain, hair loss, horror, powerlessness, weakness The enthusiasm is lowered, the appetite is lost, the headache, the thirst, the phlegm, the dry skin, etc. The stress symptom soothing or preventing agent of the present invention has the effect of relieving the above stress symptoms or preventing the occurrence of such symptoms. 126845.doc -11 · 200838496 The so-called soothing of stress symptoms means that the above symptoms are consciously or unconsciously become a normal state (consciously or without the state of the above symptoms), or close to a normal state. That is, in life, the above symptoms are perceived or judged by others. For the symptoms of individual stress in such a state, the stress disorder can be consciously or unconsciously improved by ingesting (or ingesting) the soothing agent of the present invention. ϋ In addition, the prevention of the so-called dusty symptoms of the present invention refers to the daily intake (or ingestion) in a special situation, such as a situation in which a pre-examination test or a person in front of others is expected to produce a so-called stress. The prophylactic agent of the present invention can prevent the occurrence of the above-mentioned symptoms, or reduce the frequency of occurrence (i.e., reduce the risk of the onset of stress symptoms). Moreover, the improvement of the so-called mental condition of the present invention means that although it is clearly independent of dust, In the mental state of daily life, the mental state of "the hope is improved" is improved in a good direction. As for the above-mentioned mental state of hope to improve, it can be cited as: irritability, no enthusiasm, depression, lack of happiness, lack of self-confidence, lack of Self-existence consciousness, worry, lack of concentration, over-consideration, decreased vitality, unpleasantness, depression, etc. The oxidized coenzyme Q used in the agent of the present invention can be used as previously known by the method (four), synthesis, automatic Obtained by the method of plant t extraction, but in terms of safety, it is better to use the method of synthesis The all-trans structure obtained by the method is, for example, K_ka·Coenzyme (10) (registered trademark of Kaneka Co., Ltd.). The method for obtaining the reduced coenzyme q used in the agent of the present invention is not particularly limited, for example. (4) A method of obtaining a coenzyme Q' 126845.doc -12-200838496 by a previous method, and then concentrating the reduced coenzyme Q portion in the effluent by a chromatography method, etc. In this case, 'the above-mentioned coenzyme Q can also be used as needed. A general reducing agent such as sodium borohydride or sodium disulfinate (sodium hydrogen sulfite) is added thereto, and the oxidized coenzyme Q contained in the above coenzyme Q is reduced to a reduced coenzyme Q' by a usual method and then subjected to chromatography. The method is concentrated, and it can also be obtained by a method in which the above-mentioned reducing agent is applied to the existing high-purity oxidized coenzyme Q. Alternatively, a bacterial cell containing reduced coenzyme Q or the like can also be used. Alternatively, the oxidized coenzyme Q may be reduced to a reduced coenzyme in the preparation by combining the oxidized coenzyme Q with a substance having a (four) original ability such as a vitamin. . Further, it is also possible to use the high-purity reduced coenzyme (10) which has recently been sold, that is, kaNEKA QH (Kaneka Co., Ltd. registered trademark). Further, it is also possible to use a coenzyme Q which is obtained by a known method as a mixture of an oxidized form and a reduced form.
於本發明之藥劑中’可使用氧化型辅酶Q、還原型輔酶Q 者作為其有效成分,又亦可使用作為氧化型輔 ::原型辅酶⑽混合物之辅酶Q。於此情形時,可根據盆 產印概念等適當決定辅酶Q中之 ^ ^ ^ ^ ^ 虱化1與還原型之比例。極 知地&间辅麵Q中之還原型辅 籍〜口 稀^的比例,雖然可能由於其 %疋化措施等而使成本提高,但 例如’於使用作為氧化型辅酶更尚的效果。 輔酶Q之情形時,辅酶還原型輔酶Q的混合物之 是20%以卜宙 還原型辅酶Q的比例,較好的 疋ζυ/〇以上,更好的是 於本、,更好的是鳩以上。以下, 獨之氧1 f曰早'己载為厂辅酶Q」之情形時,亦表示單 獨之乳化型辅酶Q、單猸 』π丁早 還原里辅酶Q、氧化型與還原型 126845.doc 200838496 之混合物中之任一者。 通第存在利用使用uv(ultraviolet,紫外線)檢測器之 HPLC(兩效液相層析法)系統將試料中之氧化型輔酶卩與還 原?輔酶Q加以定量,獲得其量比再算出辅酶q中之氧化型 與還原型的比例之方法;及利用於HPLC中安裝有電化學檢 測器之系統由峰面積算出氧化型辅酶Q與還原型辅酶(^的 比例之方法。於安裝有電化學檢測器之系統中,由於特異 性地測定氧化還原物質以及靈敏度較高,0而於測定生物 體,者試料中微量存在之還原型的比例之情形時,有用性 較咼。本發明中所示之氧化型辅酶Q與還原型輔酶Q之比 例’全部係由安裝有電化學檢測器之HPLd统進行定量, 當然並不限定於該方法。 本毛明之藥劑中,作為辅酶Q,較好的是使用η為1 〇之辅 酶 Q10 〇 本發明之藥劑中,可以單體形式攝取辅酶Q,但因輔酶q 為脂溶性,故較好的是將辅酶Q分散、溶解於一般食用油脂 中進行攝取。 / 至於如此的食用油脂,可舉出:植物油脂、加工油脂、 動物油脂、調合油等;具體而言,可舉出:米油、菜籽二、 棕櫚油、椰子油、玉米油、紅花油、棉籽油、芝麻油、花 生油、葵花子>'由、撖欖油、葡萄籽油、紫蘇油、食用亞: 軒油、各種堅果油、大豆油、椿油、山茶花油、茶油、月 見草油、玫瑰果油、南瓜油、紅棕櫚油、豬油、中長鏈二 酸甘油醋、牛脂、魚油及該等之混合物等;其中較=的: 126845.doc -14- 200838496 菜籽油、玉米油、 化油等植物油以及該等之混合物, 並不限定於該等。In the agent of the present invention, oxidized coenzyme Q and reduced coenzyme Q can be used as an active ingredient, and coenzyme Q which is a mixture of oxidized auxiliary :: prototype coenzyme (10) can also be used. In this case, the ratio of ^ ^ ^ ^ ^ 虱 1 to the reduced form in Coenzyme Q can be appropriately determined according to the concept of potting and printing. The ratio of the reduced-type auxiliary material to the thin-mouthed portion in the intermediate surface Q is extremely high, although the cost may be increased due to the % deuteration measures, etc., for example, the effect of using the oxidized coenzyme is more. In the case of coenzyme Q, the mixture of coenzyme-reduced coenzyme Q is 20% in proportion to the coenzyme-reducing coenzyme Q, preferably 疋ζυ/〇 or more, more preferably in the present, and more preferably in the above. . In the following, when the Oxygen 1 f曰 early 'self-contained as the coenzyme Q', it also means that the emulsified coenzyme Q alone, the monoterpene π-butyr reduction coenzyme Q, the oxidized and the reduced type 126845.doc 200838496 Any of the mixtures. Is there an oxidized coenzyme in the sample and a reduction using an HPLC (two-effect liquid chromatography) system using an uv (ultraviolet) detector? Coenzyme Q is quantified to obtain a ratio of the ratio of the oxidized form to the reduced form in the coenzyme q; and the oxidized coenzyme Q and the reduced coenzyme are calculated from the peak area by using a system equipped with an electrochemical detector in HPLC. (Method of ratio of ^. In a system equipped with an electrochemical detector, the ratio of the reduced type present in the sample to the living body due to the specific measurement of the redox species and the high sensitivity, 0 is measured. In view of the above, the usefulness of the oxidized coenzyme Q and the reduced coenzyme Q shown in the present invention is all quantified by the HPLd system equipped with the electrochemical detector, and is of course not limited to the method. In the pharmaceutical agent of the invention, it is preferred to use coenzyme Q10 having a η of 1 〇 as a coenzyme Q. In the agent of the present invention, coenzyme Q can be taken in a monomer form, but since coenzyme q is fat-soluble, it is preferred to use a coenzyme. Q is dispersed and dissolved in general edible fats and oils for ingestion. / As such edible fats and oils, there are mentioned vegetable fats, processed fats, animal fats, blending oils, and the like; Out: rice oil, rapeseed II, palm oil, coconut oil, corn oil, safflower oil, cottonseed oil, sesame oil, peanut oil, sunflower seeds > 'Y, 撖 油, grape seed oil, perilla oil, edible Asia: Xuan oil , various nut oils, soybean oil, oyster sauce, camellia oil, tea oil, evening primrose oil, rosehip oil, pumpkin oil, red palm oil, lard, medium long chain diglyceride, tallow, fish oil and mixtures thereof Of which == 126845.doc -14- 200838496 Vegetable oils such as rapeseed oil, corn oil, liquefied oil, and the like, and are not limited thereto.
水中油型乳化物之形態進行攝取。The form of the oily emulsion in water is taken up.
維生素類、茶胺酸、 轉^以外,亦可共同含有營養辅助成 或進而含有一般的食品素材。 並無特別限定,可舉出:胺基酸、金 質類、脂肪酸類、維生素B衍生物等之 γ-胺基丁酸(GABA)、甲肌肽、大豆胜 肽、硫氧化還原蛋白、小麥麩質水解物、麩醯胺酸、乳肽、 二十二碳六烯酸、二十碳五烯酸等之co-3脂肪酸、磷脂絲胺 酸、還原蝦紅素、多酚類、綠茶兒茶素、皂甙、銀杏葉萃 取物、聖約輪草、羅布麻萃取物、刺五加、山葵、芝麻素 荨木聚糖類等。 對於健康食品素材並無特別限定,可舉出:草藥類、生 藥類、簟類專或該等之萃取物。至於草藥類,例如可舉出·· 意大利香芹(flat-leaf parsley)、土木香、橄欖、牛至(〇regan〇) 、刺菜薊(cardoon)、洋甘菊、意大利蠟菊(curry piant)、貓 薄荷(catnip)、小茴香(caraway)、聖誕薔薇(Christmas rose)、 trifolium incartanum L·、天車菊(cornflower)、錦葵(maiva sylvestris)、沙拉地榆(salad burnet)、棉薰衣草(c〇tt〇n lavender)、桂皮、茉莉、甜菊、紅根草、常春菩提樹、天 竺葵、肥皂草(soapwort)、玉竹(polygonatum odoratum)、麝 126845.doc -15- 200838496 香草、艾菊、野苣(chervil)、細香蒽(chive)、豆瓣菜屬 (nasturtium)、棗、羅勒(basil)、忍冬、牛膝草(hyssop)、亞 麻、茴香、洋地黃、佈雷克萊(Brackley)蜀葵、孔雀草(tagetes patula)、金盞花(betony)、天芬菜(heliotrope)、香掛、臺灣 澤蘭(eupatorium cannabinum)、芸香、金盞花、琉璃苣 (borage)、white bo arhoimd、杉匕金镶(myrtle)、毛,蕊(verb as cum tbapsus)、馬郁蘭、薄荷、西洋蓍草(yarrow)、薰衣草、蓬 子菜(gallium verum)、檸檬草、檸檬馬鞭草(remonbabena、 檸檬香蜂草(lemon balm)、玫瑰、迷迭香、芝麻菜、野草莓、 野生三色堇(wild pansy)、勿忘草等,但並不限定於該等。 至於生藥類,例如可舉出:茜草根、阿膠、木通、兒茶、 小檗、意水、銀杏、威靈仙、茵陳蒿、茴香、薑黃、烏賊 骨、々/、烏梅、烏藥、禹餘量(limonite)、延胡索、黃耆、 黃芩、黃精、黃柏、黃連、青藤、車前草)、遠志、槐花、 海金沙(spores of Japanese climbing fem)、懷牛膝、海掉皮、 薤白、艾葉、夏枯草、花絲、何首烏、片薑黃、藿香、葛 根、滑石、芒、瓜呂根、瓜蔞子、乾薑、甘草、鱧腸、桔 梗、菊花、积殼、积實、黃檗、龜版、牛角、晃活、杏仁、 玉竹、金櫻子、銀杏、金銀花、金錢草、龍牙草(agrimonia)、 枸杞子、苦蔘、狗脊、荊芥、雞血藤、桂枝、桂皮、芡實(兮 77 )、決明子、牵牛子、玄參、飴糖、紅花、合歡皮、 降香、紅紫、香薷、香附子、厚樸、牛黃、五加皮、牛膝、 吳茱萸、胡椒、骨碎補、胡桃肉、五倍子、琥珀、牛蒡子、 芝麻、五味子、胡蘆巴、柴胡、細辛、番紅花、飛龍掌血、 126845.doc -16- 200838496 山楂、山慈兹、山梔子、蠶砂、山茱萸、胡椒、山豆根、 酸棗仁、山樂、三棱(rhizome of common burreed)、地黃、 紫苑、紫花地丁、絲瓜、地骨皮(r〇〇t-bark Chinese wolfberry)、紫根、耳石、紫石英(flu〇rhe)、紫蘇、紫蘇子、 紫蘇葉、汾梨子、地膚子、赤石脂、芍藥、蛇床子、珊瑚 菜、車前子、車前草、庶蟲、茺蔚子、砂仁、生薑、菖蒲 根、升麻、椒目、女貞子、地龍、辛夷、神麴、秦艽、沉 香、水蛭、茜草根、青箱子、青黛、青皮、石葦、赤芍、 石菖蒲、石榴皮、石決明、石膏、仙鹤草、川芎、前胡、 蟬退、旋覆花(inula flower)、川楝子、草果(tas〇k〇)、y力 クシ、草子、蒼耳子、蒼術、草豆蔻、桑白皮、桑螵蛸(mantis egg-case)、蘇木、紫蘇葉、大黃、夕彳七丰シ十、大青葉、 大棗、大腹皮、澤瀉、澤蘭、丹參、竹茹、竹萌(千夕七々)、 知母、鉤藤、豬苓、陳皮、葶藶子(seed 〇f pepperweed)、 天花粉、天竺黃、天南星、天麻、天冬、冬瓜子、當歸、 燈心、冬蟲夏草、獨活、祧仁、菟絲子、杜仲、肉蓰蓉、 肉豆蔻、乳香、人蔘、忍冬、女貞、白芥子、麥芽、柏子 仁、白豆蔻、白鮮皮(roo卜bark of deusufruit pittany)、白頭 翁、白扁豆(white hyacinth bean)、麥門冬、巴戟天、薄荷 北沙參、半夏、番紅花、皮糠、荸薺、百合、白芷、白術、 白檀、白薇、百部根、白花蛇”、白及、白僵蠢、檳7榔 子、覆盆子、茯茶、附子、f甲(turtle shell)、紅花、扁蓄、 防己、茅根、防風、蒲黃、蒲公英、補骨脂、牡丹皮、牡 蠣、玫瑰、麻黃、麻黃根、麻子仁、蔓荊子、蜜蒙花、呵 126845.doc •17- 200838496 梨勒(termmalia chebura retz)、木通、木賊、木瓜、木未、 藥壺、益知、益母草'夜交藤、熊膽、薏仁、善燃草、雷 丸、萊菔子、羅漢果、龍眼肉、奇蒿、龍骨、龍膽、高良 薑、綠豆、連翅、連錢草、彎肉、鹿茸、露蜂房等’但並 不限定於此。作為洋蒜類,可舉出:松茸、舞茸、香兹、 朴樹.、叢生口磨、雪茸、長齒白齒耳g(myeGiept。— aitchisonii)等。 本發明之樂劑中除_Q以外,亦可_同含有抗氧化物質 對於抗氧化物質並無特別限定,例如可舉出: 維生素E衍生物、維生素c、維生素C衍生物、番 ^素、維生素A、類胡蘿蔔素類、維生素B、維生辛B衍 生物、類黃_類、麵胱甘肽、還原瑕紅素、砸等。 又,對於抗氧化酶並無特別限定,例如可舉出 = _)、麵胱甘肽過氧化酶,甘“轉移酶、 麵耽甘狀還原酶、過氧化氫酶、抗壞血酸__轉移酶 本發明之藥劑’亦可於其中適當組合 上所例示之抗氧化物質、抗氧化酶、一種以上以 食品素材而加以使用。 S 成分、健康 本發明之藥劑中,進而除上述成 適當添加混合作為藥劑學或。 ’、可利用常法 於如此素龍無特職例如=許㈣他素材。對 潤滑劑、黏合劑、抗氧化劑:出.賦形剤、崩散劑、 進劑、溶解輔助劑、穩定化 :’1、抗凝集劑、吸收促 對於上述賦形劑並無特/強壯成分等。 疋,例如可舉出:白糖、乳 126845.doc -18- 200838496 糖、葡萄糖、玉米殿粉、甘露醇、杜曰 硫酸鈣等。 、’、。曰曰纖維素、磷酸鈣、 對於上述崩散劑並無特別限定, s匕#讲^ J如可舉出:澱粉、瓊 月曰、#棣酸鈣 '碳酸鈣、碳酸氫鋼、 叛甲基纖維素、黃箸膠等。 糊精、結晶纖維素、 對於上述潤滑劑並無特別限定, 硬脂酸鎂,二醇、二― 對於上述黏合劑並無特別限定, .m ^ 1 J如可舉出:乙基纖維 素、甲基纖維素、羥丙基曱基纖維素 ^ ^ ^ 頁蓍膠、蟲膠、明 膠、阿拉伯膠、聚乙烯吡咯烷酮、 枣田直二π # t乙稀醇、聚丙烯酸、 汆甲基丙烯酸、山梨糖醇等。 對於上述抗氧化劑並無特別限定, ^ , ^ v ^ 例如可舉出:抗壞血 酉夂、生月酚、維生素A、β·胡蘿蔔素、 舻铷 ^ ^ ^ ^ ’、亞肌酸氫鈉、硫代硫 酉文納、焦亞酸納、檸:樣酸等。 對於上述著色劑並無特別限定, 於醫藥品中者ρ 例如可使用被容許添加 對於上述抗凝集劑並無特別限定, 滑石粉、輕質無水料、含水二氧化二可等舉出:硬脂酸、 /於上述吸收促進劑並無特別限定,例如可舉出:高級 醇類、鬲級脂肪酸類、或卵磷脂、溶血 、门 酸酉旨等界面活性劑等。 9 Λ甘油脂肪 對於上述溶解辅助劑並無特別限定, ^ 例如可舉出:黾夾 酸、琥珀酸、蘋果酸等有機酸等。 巧木 對於上述穩定化劑並無特別限定,例如 J举出··苯甲酸、 126845.doc -19- 200838496 苯甲酸鈉、對羥苯甲酸乙酯等。 例如可舉出··肌酸、 、胺基酸以及該等物 對於滋養強壯成分並無特別限定, 牛磺酸、維生素m、維生素B衍生物 貝之處合物。 本發明之藥劑或者含有該藥劑之組人 品、健康食品、營養輔助食0 σ於食 考物人σ ^輔助“、補充品、醫藥品、準藥品、 月1物& °σ、或者飼料之用途。此處所袖# # a β 此處所明健康食品,係指除In addition to vitamins, theanine, and the like, it may also contain nutrient-assisted or further general food materials. The γ-aminobutyric acid (GABA), the carnosine, the soybean peptide, the sulfur redox protein, and the wheat bran such as amino acid, gold, fatty acid, and vitamin B derivative are mentioned. Hydrolyzate, glutamic acid, lactopeptide, docosahexaenoic acid, eicosapentaenoic acid, etc., co-3 fatty acid, phospholipidic acid, reduced astaxanthin, polyphenols, green tea , saponin, ginkgo leaf extract, sacred grass, apocynum extract, acanthopanax senticosus, wasabi, sesamin xylan and so on. The health food material is not particularly limited, and examples thereof include herbal medicines, biopharmaceuticals, anthraquinones, or the like. As for the herbs, for example, flat-leaf parsley, earthy wood, olive, oregano, cardoon, chamomile, curry piant, Catnip, caraway, Christmas rose, trifolium incartanum L., cornflower, malva sylvestris, salad burnet, cotton lavender 〇tt〇n lavender), cassia, jasmine, stevia, red root grass, primrose, geranium, soapwort, polygonatum odoratum, 麝126845.doc -15- 200838496 vanilla, tansy, chicory ( Chervil), chive, nasturtium, jujube, basil, honeysuckle, hyssop, flax, fennel, digitalis, brackley hollyhock, peacock (tagetes patula), betony, heliotrope, incense, eupatorium cannabinum, musk, calendula, borage, white bo arhoimd, myrtle, , verb as cum tbapsus, marjoram, mint, yarrow, lavender, gallium verum, lemongrass, lemon verbena (remonbabena, lemon balm, rose, Rosemary, arugula, wild strawberry, wild pansy, forget-me-not, etc., but not limited to such. For the raw medicine, for example, valerian root, donkey-hide gelatin, Mutong, catechu, Xiaoyan, Yishui, Ginkgo biloba, Clematis, Artemisia scoparia, Fennel, Turmeric, Cuttlefish, Begonia, Ume, Black Medicine, Limonite, Corydalis, Astragalus, Astragalus, Polygonatum, Phellodendron, Huanglian, Qingteng, plantain), Yuanzhi, 槐花, sea golden sand (spores of Japanese climbing fem), Achyranthes bidentata, sea off skin, white stalk, wormwood, Prunella vulgaris, filigree, Polygonum, turmeric, musk, puerarin, Talc, mango, melon root, melon seed, dried ginger, licorice, sputum, platycodon, chrysanthemum, crust, solid, scutellaria, turtle, horn, sway, almond, polygonatum, sakura, ginkgo, Honeysuckle, Lysimachia, Atoll (agr) Imonia), scorpion, bitter, dog ridge, schizonepeta, spatholobus, cassia twig, cinnamon, medlar (兮77), cassia seed, taurus, scrophularia, sugar, safflower, acacia, scent, red purple, toon , Xiangfuzi, Magnolia, Niuhuang, Wujiapi, Achyranthes, Wusong, Pepper, Drynaria, Walnut, Galla, Amber, Burdock, Sesame, Schisandra, Fenugreek, Bupleurum, Asarum, Saffron , 飞龙掌血, 126845.doc -16- 200838496 Hawthorn, Shanzizi, Hawthorn, Silkworm, Hawthorn, Pepper, Soybean Root, Suanzaoren, Shanle, Rhizome of common burreed, Rehmannia, Aster , purple diced, loofah, bone skin (r〇〇t-bark Chinese wolfberry), purple root, otolith, amethyst (flu〇rhe), perilla, perilla, perilla leaf, avocado, kochia, azurite Fat, peony, Cnidium, Coral, Psyllium, Plantain, Aphid, 茺 子, Amomum, Ginger, Calamus, Cimicifuga, Peony, Ligustrum, Dilong, Xinyi, Shenque, Qin , agarwood, leeches, valerian roots, green boxes, barley, green skin Dendrobium, red peony, sarcophagus, pomegranate peel, stone cassia, gypsum, crane grass, Chuanxiong, Qianhu, 蝉 、, inula flower, Chuanxiongzi, grass fruit (tas〇k〇), y force, grass, cocklebur, atractylodes, tortoise, mulberry, mulberry (mantis egg-case), hematoxylin, perilla leaf, rhubarb, 夕彳七丰シ10, Daqingye, jujube , Big belly skin, Alisma, Zeeland, Salvia, Zhuru, Zhu Meng (千夕七々), Zhimu, Uncaria, Pork, Chenpi, 葶苈子 (seed 〇f pepperweed), Tianhua powder, Tianzhu yellow , Tiannanxing, Tianma, Asparagus, Winter melon seeds, Angelica, Dengxin, Cordyceps sinensis, Duhuo, Huanren, Cuscuta, Eucommia, Cistanche, Nutmeg, Frankincense, Mantis, Honeysuckle, Nvwa, White mustard, Malt, Baiziren, white cardamom, white fresh skin (roo bark of deusufruit pittany), pulsatilla, white lentils (white hyacinth bean), maimen winter, basmati, mint northern ginseng, pinellia, saffron, pimple,荸荠, lily, white peony, atractylodes, white sandalwood, white virgin, hundred roots, white flower snake, white and white Stupid, betel nut 7, raspberry, scented tea, aconite, f (turtle shell), safflower, stagnation, anti-self, maogan, wind, pudding, dandelion, psoralen, peony bark, oyster, rose, ephedra , Ephedra root, Maziren, Viburnum, honey, flower, 126845.doc •17- 200838496 pear (termmalia chebura retz), Mutong, wood thief, papaya, wood, medicine pot, Yizhi, motherwort' Night vine, bear bile, coix seed, good burning grass, Lei Wan, Laiwuzi, Luo Han Guo, Longan meat, Artemisia, keel, gentian, galangal, mung bean, wing, even money grass, bent meat, antler, dew The hive, etc. 'but is not limited to this. Examples of the yam are: pine velvet, maitake, fragrant sage, hackberry, clumping mouth, snow velvet, and long tooth white tooth g (myeGiept. - aitchisonii). In addition to _Q, the antioxidant of the present invention may be an antioxidant substance, and the antioxidant substance is not particularly limited, and examples thereof include vitamin E derivatives, vitamin C, vitamin C derivatives, and vitamins. Vitamin A, carotenoids, vitamin B, vitamin B derivatives, yellowoids, glutathione, reduced ruthenium, guanidine and the like. Further, the antioxidant enzyme is not particularly limited, and examples thereof include _), a glutathione peroxidase, a glycotransferase, a glucoside reductase, a catalase, and an ascorbate __transferase. The agent of the invention may be used in combination with an antioxidant substance or an antioxidant enzyme exemplified above, and one or more of them may be used as a food material. S component, health, and the agent of the present invention may be appropriately added and mixed as a drug in addition to the above. Learn or. ', can use the common law in such a dragon without special duties such as = Xu (four) his material. For lubricants, adhesives, antioxidants: out. Shaped 剤, disintegrating agent, injection, dissolution aid, stability For the above-mentioned excipients, there are no special/strong ingredients, etc. 疋, for example, white sugar, milk 126845.doc -18- 200838496 sugar, glucose, corn house powder, Mannitol, rhododendron calcium sulfate, etc., ', 曰曰 cellulose, calcium phosphate, and the above disintegration agent is not particularly limited, s匕# speaks, for example, J: starch, Qiongyue, #棣酸Calcium calcium carbonate, hydrogen carbonate steel, betrayal methyl The cellulose, the ceresin, etc. The dextrins and the crystalline cellulose are not particularly limited, and the magnesium stearate, the diol, and the second binder are not particularly limited, and the m ^ 1 J can be used. For example: ethyl cellulose, methyl cellulose, hydroxypropyl fluorenyl cellulose ^ ^ ^ page gum, shellac, gelatin, gum arabic, polyvinylpyrrolidone, jujube straight two π # t ethyl alcohol, Polyacrylic acid, hydrazine methacrylic acid, sorbitol, etc. The above antioxidant is not particularly limited, and ^ , ^ v ^ may, for example, be ascorbic acid, raw phenol, vitamin A, beta carotene,舻铷^ ^ ^ ^ ', sodium creatine hydride, thiosulfanone, sodium pyrophosphate, lemon: acid, etc. The coloring agent is not particularly limited, and may be used, for example, in pharmaceuticals. The anti-aggregation agent is not particularly limited, and the talc powder, the light anhydrous material, and the aqueous dioxide may be, for example, stearic acid or the above-mentioned absorption enhancer is not particularly limited, and examples thereof include, for example, : Higher alcohols, terpene fatty acids, or lecithin, hemolysis, acid In the case of the above-mentioned dissolution aid, the above-mentioned dissolution aid is not particularly limited, and examples thereof include organic acids such as argonic acid, succinic acid, and malic acid. There is no particular limitation, for example, J. benzoic acid, 126845.doc -19-200838496 sodium benzoate, ethyl p-hydroxybenzoate, etc. Examples include creatinine, amino acids, and the like for nourishment. The strong component is not particularly limited, and the taurine, the vitamin m, and the vitamin B derivative are compounded. The agent of the present invention or the group containing the drug, the health food, and the nutritional supplement 0 σ in the food test object σ ^ auxiliary ", supplements, pharmaceuticals, quasi-drugs, month 1 & ° σ, or the use of feed. Here the sleeve # # a β The health food here means
»建康艮品以外,健康輔助食品、特定保健用食品、營 :機,食品等除藥品以外用以維持健康而可攝取之所有食 :形態。X ’於食品為所謂健康食品之情形時,可舉出將 氧化里輔酶Q及/或還原型輔酶Q以每丨次服用的攝取單位量 2形怨進行包裝之形態等,於食品為健康飲料之情形時, I舉出有將使該輔酶Q懸浮或溶解之飲料以每丨次飲完之形 態裝入瓶等中之形態。 所明每1次之攝取單位量,係指於食品之情形時所攝取之 有效成分量。特別是於食品之情形時,食品整體之攝取量 存在個人差異,作為組合物中之有效成分之含量,難以一 概地加以規定,因此考慮到下述每1天之有效攝取量,推薦 以有效成分的1次攝取量來加以規定。該1次攝取量,係根 據年齡、體重、性別、壓力程度等而有適當變動之量。再 者’於醫藥品之情形時,可舉出含有1次攝取量即1次投與 的有效成分量之經包裝之形態,或以每丨次飲完之形態裝入 瓶等中之形態。 對於本發明之藥劑或者含有該劑之組合物之形態並無特 126845.doc -20- 200838496 別限定,可舉出:膠囊劑、微膠囊劑、軟膠囊劑 散劑、咀嚼製劑、糖聚、液劑等可經口攝取之料· j 油脂組合物、調理油類、噴油類、黃油類、人::、’食用 起穌油類、泡沫乳油類、濃縮乳類、白化劑類、;::、、 泡采液類、麵包類、蛋糕類、㈣類、曲奇類、、、 類、點心類'油點心類、巧$六 工點〜 5克力及巧克力點心類、米餅類、»In addition to Jiankang products, health foods, foods for specific health care, camps, food, food, etc., all foods that are healthy and ingestible except for medicines: form. In the case where the food is a so-called healthy food, a form in which the oxidized coenzyme Q and/or the reduced coenzyme Q are packaged in an intake unit amount of 2 times per ounce is used, and the food is a healthy drink. In the case of the case, the beverage in which the coenzyme Q is suspended or dissolved is put into a bottle or the like in a form of being drunk every time. It is to be noted that the amount of the unit intake per one time refers to the amount of the active ingredient taken in the case of food. In particular, in the case of foods, there is a personal difference in the overall intake of the food, and it is difficult to specify the content of the active ingredient in the composition. Therefore, it is recommended to use the active ingredient in consideration of the following effective intake per day. The amount of intake is specified once. The amount of this intake is appropriately changed depending on the age, body weight, sex, degree of stress, and the like. In the case of the pharmaceutical product, the form of the package containing the amount of the active ingredient once administered once, or the form of being filled into a bottle or the like in the form of one drink per serving, may be mentioned. The form of the agent of the present invention or the composition containing the same is not specifically limited to 126845.doc -20-200838496, and examples thereof include a capsule, a microcapsule, a soft capsule powder, a chewable preparation, a sugar polymerization, and a liquid. Agents, etc., which can be taken orally. j Oil composition, conditioning oil, fuel oil, butter, human::, edible edible oil, foamed emulsifiable concentrate, concentrated milk, whitening agent, :,, bubble liquid, bread, cake, (four), cookies,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,
油炒麵粉類、醬料類、調味汁類、配菜類、冰點類、麵類、 混合麵團類、油炸食品類、加工肉產品類、水產囊產口類 冷盤類、畜產冷柬食品、農產冷;東食品等冷來食品二、米 飯類、果醬類、乳路、乳路食品、類乳路食品、膠類、糖 2類、醱酵乳類、罐裝類、飲料類等作為一般食品之形態; 藉由貼附劑、乳液、噴霧等外皮,將有用成分送入體:之 形態等。 進而,可藉由與草藥、生藥成分等芳香療法巾所使用之 成分加以組合,或者與攝取本中請案之壓力症狀舒緩或預 防劑同時併用芳香療法、洗澡、按摩、音樂鑒賞、香黨、 動物療法、步行等放鬆方法等,而期待更強的效果。0 含有本發明之藥劑之組合物每丨天的有效攝取量以還原 型輔酶Q10之量計,為10〜5〇〇 mg,較好的是5〇〜3〇〇 mg, 更好的是50〜200 mg。於攝取量為5〇 mg以上之情形時,可 充分地獲得由於壓力所導致症狀之舒緩或預防作用、精神 狀況之改善效果。 上述有效攝取量,以氧化型辅酶Q1〇之量計,為5〇〜1〇〇〇 mg ’較好的是100〜600 mg,更好的是2〇〇〜35〇 mg。於攝取 126845.doc -21 - 200838496 1為200 mg以上之情形時,可充分地獲得由㈣力所導致 症狀之舒缓或預防作用、精神狀況之改善效果。但是 =知有該等攝取量根據㈣的劑型而不同,若為高吸 裝劑,則亦可期待以更低的攝取量達成特定之目的。 並:攝取量可1曰1次或1曰分成數次攝取。對於攝取期間 並純別限定’通常為2週以上,較好的是i個月以上”寺 別疋’於作為Μ力症狀之預防劑而攝取之情形時,於Oil-fried flour, sauces, sauces, side dishes, ice-creams, noodles, mixed doughs, fried foods, processed meat products, cold-growing products of aquatic products, cold foods for livestock, Cold food for agriculture; cold foods such as East food, rice, jam, milk road, milk road food, milk-like food, rubber, sugar, fermented milk, canned food, beverage, etc. The form of the food; the form of the useful ingredient is sent to the body by means of a patch, an emulsion, a spray, and the like. Furthermore, it can be combined with ingredients used in aromatherapy towels such as herbal medicines and crude medicine ingredients, or combined with aromatherapy, bathing, massage, music appreciation, and fragrant party, together with the stress symptom soothing or preventive agent in the case of ingestion. Animal therapy, walking and other relaxation methods, etc., and expect a stronger effect. The effective intake of the composition containing the agent of the present invention per day is 10 to 5 mg, preferably 5 to 3 mg, more preferably 50, based on the amount of reduced coenzyme Q10. ~200 mg. When the intake is 5 〇 mg or more, the soothing or preventive effects of the symptoms caused by the stress and the improvement of the mental condition can be sufficiently obtained. The above effective intake is 5 〇 1 to 1 mg, preferably 100 to 600 mg, more preferably 2 to 35 mg, based on the amount of the oxidized coenzyme Q1. When ingesting 126845.doc -21 - 200838496 1 is 200 mg or more, the effect of the relief or prevention of the symptoms caused by (4) force and the improvement of mental state can be sufficiently obtained. However, it is known that these intakes differ depending on the dosage form of (4), and if it is a high-absorbent, it is expected to achieve a specific purpose with a lower intake. And: the intake can be divided into several times in 1 or 1 time. In the case of the ingestion period, it is usually limited to 'usually 2 weeks or more, and preferably more than i months or more, when the temple is ingested as a preventive agent for stress symptoms,
症狀之狀況前,較好的是預先至少攝取1週本發 因並未發現辅酶Q具有蓄積性,故本發明之藥劑會由於攝 取結束而使其效果減弱。因此,於期待舒緩壓力症狀或改 善精神狀況期間’或者於預測產生壓力症狀期間,較 是曰常性攝取。 本發明之藥劑可用於舒緩或預防人、人以外的動物[例 如,人以外之哺乳類(豬、牛、馬、狗、猶等之家畜及玩賞 動物)、雞等鳥類等]之上述壓力症狀’或者用於改善精神二 況0 本發明提供-種舒緩或預防上述壓力症狀之方法或者改 善精神狀況之方法’該方法包含:向該必須加以舒緩、預 防或改善之投與對象(例如,人或人以外之動物),較好的是 曰常自覺或他覺上述壓力症狀之投與對象、或者希望改2 精神狀況之投與對象,投與有效量的上述式(丨)所表示之^ 化型辅酶Q及/或上述式(2)所表示之還原型辅酶Q之步驟^ 本發明進一步提供一種用以實施上述方法之商業包妒。 126845.doc -22- 200838496 該商業包裝包含上述式⑴所表示之氧化型輔酶Q及/或上述 式(2)所㈣之還原型_Q,進而包含記載有可將該輔酶q 使用(或應使用)於舒緩或預防上述壓力症狀或者改善精神 狀況等之記載物(例如,用以實施上述方法之指示書 作為其他態樣,本發明提供—㈣以製造壓力症狀之舒 緩或預防劑、或者精神狀況之改善劑的上述式⑴所表示之 氧化型辅酶Q及/或上述式⑺所表示之還原型輔酶q之用 途。 [實施例] 其次,根據實施例更詳細地說明本發明,但本發明並不 僅限定於該實施例。 (實施例1)氧化型辅酶Q10對於自覺壓力之健康人之緊 張或者精神壓力之舒緩效果 以雙盲試驗之交叉法來評價氧化型輔酶Q1〇對於自覺壓 力之健康志願者之效果。預先以Visual alan〇g 8_(咖, 視覺類比量表)測定健康志願者之疲勞感(精神壓力程度), 將自覺有某種程度壓力之志願者加以區分。VAS(視覺類比 量表)’係將在具有丨〇 cm長度之線段兩端記有成為基準之 表見(將無症狀或s忍為农低程度作為左端,將最高程声作為 t端)的紙給被測試者看,將被測試者當前之狀態表示於線 段上,以測定主觀疲勞感或症狀。例如作為自覺壓力之評 價’可將直線左端作為「完全無壓力」,將右端作為「經 驗且獲得之最大壓力」’係藉由使被測試者將當前的狀態 標註於線段上,測定距離線段左端之長度,而評價自覺壓 126845.doc -23- 200838496 力之程度。將所選的志願者26人分成二群,讓其攝取一週 具有表1記載的製劑組成之氧化型辅酶Q10膠囊(被測試食) 或者安慰劑膠囊(對照食),每天攝取2粒膠囊(於被測試食品 之情形時,氧化型輔酶Q10攝取量為200 mg/曰),同樣地利 用VAS將攝取前後之各種症狀(7個項目:自覺壓力、緊張 - 度、嗜睡、疲倦程度、意慾、口渴、焦躁感)。進而,實施 • 作業效率(行為效率)之評價即Advanced Trail making test (ATMT,高級連線測驗)。又,血中CoQlO量,亦係於攝取 • 前後進行採血,利用HPLC進行定量。 [表1] 試驗食組成表(每1粒4-圓形軟膠囊) 成分組成 被測試食 對照食 氧化型輔酶Q1 〇(mg) 100 - 紅花油(mg) 134.67 234.67 蜂躐(mg) 4.33 4.33 POEM S-lOO(mg) 0.6 0.6 大豆卵鱗脂(mg) 0.4 0.4 氧化型辅酶Q10 : Kaneka股份有限公司製造 紅花油:Nisshin-oillio股份有限公司製造 黃蜜蠟··三木化學工業股份有限公司製造 POEM S-1 00 :甘油脂肪酸酯系界面活性劑,理研維生素 股份有限公司製造 大豆卵礙脂:Tsuji_seiyu股份有限公司製造 VAS之結果示於表2。於氧化型輔酶Q10攝取群中,於緊 張度及焦躁感中發現有統計學上有意的(p<(K〇5)舒緩,於自 126845.doc -24· 200838496 覺性壓力及口渴中發現有舒缓傾向(p<0·5)。另一方面’認 為嗜睡、意慾及疲倦程度中’於氧化型輔酶Q10攝取群與安 慰劑群之間並未發現有差別。進而,ATMT之性能中,發現 反應時間之有意的縮短,顯示藉由攝取氧化型辅酶Q10而提 高作業效率。先前之抗壓力物質中’大多伴有使行為降低 之鎮靜作用,於實際使用中會成為問題,但該等結果顯示, ^ 氧化型輔酶Q10之壓力舒缓效果並不伴有鎮靜作用’有用性 較高。 * [表 2] VAS之主觀評價值 試料 攝取前 攝取後 緊張度 安慰劑 3·64 土 1.49 3.46±1·50 氧化型輔酶Q10 3·64±1·39 3.05士 1.59** 焦躁感 安慰劑 3.63 士 1.60 3.53±1.51 氧化型辅酶Q10 3.88 土 1.55 3.07 士 1.75** 自覺性壓力 安慰劑 4.09 士 1.67 3.66±1.77 氧化型輔酶Q10 4.29±1.83 3.26 土 1·74* 口渴 安慰劑 5.14 士 1.59 4.79 士 1.68 氧化型輔酶Q10 4.97±1.39 4.51±1.61* 嗜睡 安慰劑 4.80±1.46 4.32 士 1.88 氧化型輔酶Q10 4.86 土 1.59 4.23 土 1.85 意慾 安慰劑 4·96±1·24 4.79 土 1.36 氧化型輔酶Q10 4.86±1.17 4·61 土 1.59 疲倦度 安慰劑 3.74±1.26 3.57 士 1.76 ,氺氺 氧化型輔酶Q10 3·96±1·52 3.55 土 1.70 *ρ<0.5 ’ **ρ<〇·〇5相對於student t-test placebo群之有意差 本試驗中之血漿中輔酶Qi〇濃度,相對於攝取前為 986·6±914·1 nmol/L,攝取後為 3679.4土1652.7 nmol/L 約增 加至3.7倍。 126845.doc -25 - 200838496 (K施例2)還原型辅酶Q1〇對自覺壓力之健康人之緊張 或者精神壓力之舒緩效果 以與實%例1同樣之方式,以雙盲試驗之交叉法來評價還 原里辅酶Q10對於自覺有壓力之健康志願者之效果。將自覺 有壓力之健康志願者26人分成兩群,一週每日攝取1粒膠囊 之具有表3兄載的製劑組成之還原型辅酶Q1〇膠囊(其中,使 用3有約1重1 %之氧化型輔酶Q1〇之還原型輔酶Qi〇)(被 忒驗艮)或者安慰劑膠囊(對照食),利用VAS將攝取前後之 疲勞感加以定量,以ATMT將行為效率加以定量。已知有還 原型辅酶Q10之經口吸收性好於氧化型輔酶Q1〇,因此進行 預備研究,將獲得與攝取2〇〇 mg氧化型辅酶Q1〇相同程度的 血中/辰度之50 mg設定為還原型辅酶q1〇之一天的攝取量。 〜果獲彳于與攝取2〇〇 mg氧化型輔酶q1〇類似的結果,具 體而&,發現緊張度、焦躁感及自覺性壓力中有統計學上 有意的舒緩同時發現ATMT之行為之改善。另一方面,於嗜 睡、思慾及疲倦度中,發現還原型辅酶Q丨〇攝取群與安慰劑 群之間並無差別。其結果顯示,還原型辅酶Q10之壓力舒緩 效果並不伴有鎮靜作用,有用性較高,同時與氧化型輔酶 Ql〇相比較,證明以較低用量發現有同等效果。 126845.doc 26 - 200838496 [表3] 試驗食組成表(每1粒‘圓形軟膠囊) 成分組成 b 型輔酶Q10(mg) 對照^ 50 - (包含1重量%氧化型辅酶Q10) 紅花油(mg) /1 〇 ο 蜂蠟(mg) 184.67 POEM S-lOO(mg) 4.33 |大豆卵碟脂(mg) 0.6 --—---- A Λ 0.6 υ·4 ----- 0.4Before the symptom state, it is preferred that the coenzyme Q is not accumulated for at least one week in advance, and therefore the agent of the present invention is weakened by the end of the administration. Therefore, during the period of expecting to relieve stress symptoms or improve mental status, or during the prediction of stress symptoms, it is more common. The agent of the present invention can be used for soothing or preventing animals other than humans and humans [for example, the above-mentioned stress symptoms of mammals other than humans (pig, cow, horse, dog, domestic animals and animals), chickens and the like] Or for improving mental condition. The present invention provides a method for soothing or preventing the above-mentioned stress symptoms or a method for improving a mental condition. The method includes: administering to a subject (for example, a person or a person who must be relieved, prevented or improved) It is better for the animal other than the human being to consciously or for the above-mentioned stress symptoms, or for the target of the mental state, and to cast an effective amount of the above formula (丨) The step of the coenzyme Q and/or the reduced coenzyme Q represented by the above formula (2). The present invention further provides a commercial package for carrying out the above method. 126845.doc -22- 200838496 The commercial package comprises the oxidized coenzyme Q represented by the above formula (1) and/or the reduced form _Q of the above formula (2) (4), and further comprises the description that the coenzyme q can be used (or The use of the article for relieving or preventing the above-mentioned stress symptoms or improving the mental condition (for example, the instructions for carrying out the above method as other aspects, the present invention provides - (iv) to provide a soothing or preventive agent for stress symptoms, or a spirit The use of the oxidized coenzyme Q represented by the above formula (1) and/or the reduced coenzyme q represented by the above formula (7) in the condition improving agent. [Examples] Next, the present invention will be described in more detail based on examples, but the present invention It is not limited to this embodiment. (Example 1) Oxidation-type coenzyme Q10 The stress-relieving effect of stress or mental stress on a healthy person with self-consciousness is evaluated by the double-blind test method to evaluate the health of oxidative coenzyme Q1〇 for conscious stress. The effect of volunteers. Pre-test the fatigue of healthy volunteers (degree of mental stress) with Visual alan〇g 8_ (cafe, visual analog scale), will consciously have some kind of Volunteers of degree pressure are distinguished. The VAS (Visual Analog Scale) will be recorded as a benchmark at both ends of the line with a length of 丨〇cm (the asymptomatic or s will endure the low degree of agriculture as the left end, The highest-range sound is taken as the t-end paper to the testee, and the current state of the testee is indicated on the line segment to determine the subjective fatigue or symptoms. For example, as the evaluation of the conscious pressure, the left end of the straight line can be regarded as "completely "Pressure", the right end is regarded as "experience and maximum pressure obtained" by letting the testee mark the current state on the line segment, and measuring the length of the left end of the distance segment, and evaluating the conscious pressure 126845.doc -23- 200838496 The degree of the selected volunteers was divided into two groups, and they were inoculated with oxidized coenzyme Q10 capsule (tested food) or placebo capsule (control food) having the composition of the preparation described in Table 1 for 2 capsules per day. Capsule (in the case of the food to be tested, the oxidized coenzyme Q10 intake is 200 mg / 曰), the same symptoms are used before and after the intake of VAS (7 items: conscious pressure, tight Zhang-degree, lethargy, fatigue, desire, thirst, and anxiety. Further, the implementation of the operational efficiency (behavior efficiency) is the Advanced Trail making test (ATMT). In addition, the blood CoQlO The amount is also measured by ingestion. Blood is collected before and after, and quantified by HPLC. [Table 1] Test composition table (one round of 4-round soft capsule) Composition of the test food control oxidized coenzyme Q1 〇 (mg) 100 - Safflower oil (mg) 134.67 234.67 Bee sting (mg) 4.33 4.33 POEM S-lOO(mg) 0.6 0.6 Soybean egg yolk (mg) 0.4 0.4 Oxidized coenzyme Q10: Kaneka Co., Ltd. safflower oil: Nisshin-oillio Co., Ltd. manufactures yellow beeswax··Miki Chemical Industry Co., Ltd. manufactures POEM S-1 00: glycerin fatty acid ester surfactant, Riken Vitamin Co., Ltd. manufactures soybean egg liposuction: results of VAS manufactured by Tsuji_seiyu Co., Ltd. Shown in Table 2. In the oxidized coenzyme Q10 ingestion group, statistically intentional (p<(K〇5) soothing was found in the tension and eschar of sensation, which was found in conscious stress and thirst from 126845.doc -24· 200838496 The tendency to soothe (p<0.5). On the other hand, 'the level of drowsiness, desire, and fatigue' was not found to differ between the oxidized coenzyme Q10 ingestion group and the placebo group. Further, in the performance of ATMT, It was found that the intentional shortening of the reaction time showed that the work efficiency was improved by taking up the oxidized coenzyme Q10. Most of the previous anti-stress substances were accompanied by a sedative effect of lowering the behavior, which would become a problem in actual use, but the results were It is shown that ^ The pressure-relieving effect of oxidized coenzyme Q10 is not accompanied by sedation. 'There is higher usefulness. * [Table 2] Subjective evaluation value of VAS Samples before ingestion Tension after placebo 3·64 Soil 1.49 3.46±1 ·50 oxidized coenzyme Q10 3·64±1·39 3.05±1.59** eschar sensitizing placebo 3.63 士 1.60 3.53±1.51 oxidized coenzyme Q10 3.88 soil 1.55 3.07 士 1.75** conscious pressure placebo 4.09 士 1.67 3.66 1.77 Oxidized Coenzyme Q10 4.29±1.83 3.26 Soil 1.74* Thirsty Placebo 5.14 ± 1.59 4.79 ± 1.68 Oxidized Coenzyme Q10 4.97±1.39 4.51±1.61* Sleepy Placebo 4.80±1.46 4.32 ±1.88 Oxidized Coenzyme Q10 4.86 Earth 1.59 4.23 soil 1.85 intended placebo 4·96±1·24 4.79 soil 1.36 oxidized coenzyme Q10 4.86±1.17 4·61 soil 1.59 fatigue placebo 3.74±1.26 3.57 ± 1.76, 氺氺 oxidized coenzyme Q10 3·96 ±1·52 3.55 soil 1.70 *ρ<0.5 ' **ρ<〇·〇5 relative to the student t-test placebo group. The concentration of coenzyme Qi in the plasma in this test is 986·6 before ingestion. ±914·1 nmol/L, after ingestion, 3679.4 soil 1652.7 nmol/L increased to approximately 3.7 times. 126845.doc -25 - 200838496 (K Example 2) Reduced coenzyme Q1〇 is stressful to healthy people with conscious stress or The soothing effect of mental stress In the same manner as in Example 1, the cross-over method of double-blind test was used to evaluate the effect of coenzyme Q10 in reducing stress on healthy volunteers who were consciously stressed. Twenty-six healthy volunteers who were consciously stressed were divided into two groups, one capsule per day, one capsule of the reduced coenzyme Q1 capsule containing the preparation of the table 3 brothers (wherein 3 used 1 to 1% oxidation) The coenzyme Q1〇 reduced coenzyme Qi〇) or placebo capsule (control diet) was quantified by VAS before and after ingestion, and the behavioral efficiency was quantified by ATMT. It is known that the reductive coenzyme Q10 is better than the oxidized coenzyme Q1〇, so a preliminary study will be carried out to obtain a blood/increase 50 mg setting equivalent to the intake of 2 mg of oxidized coenzyme Q1〇. It is the intake of the reduced coenzyme q1 for one day. ~ The fruit was found to be similar to the result of ingesting 2 mg of oxidized coenzyme q1 ,, specifically, &, found statistically intentional soothing in tension, eschar and conscious stress and found improvement in ATMT behavior . On the other hand, in the levels of sleepiness, thought and fatigue, there was no difference between the reduced coenzyme Q丨〇 intake group and the placebo group. The results showed that the pressure-relieving effect of the reduced coenzyme Q10 was not accompanied by sedative effect, and the usefulness was high, and compared with the oxidized coenzyme Ql ,, it was confirmed that the effect was found at a lower dose. 126845.doc 26 - 200838496 [Table 3] Test food composition table (per round 'soft capsules') Composition b-type coenzyme Q10 (mg) Control ^ 50 - (containing 1% by weight of oxidized coenzyme Q10) Safflower oil ( Mg) /1 〇ο Beeswax (mg) 184.67 POEM S-lOO(mg) 4.33 | Soybean egg fat (mg) 0.6 ------- A Λ 0.6 υ·4 ----- 0.4
紅花油:Nisshin-omio股份有限公司製造 蜂蝶·二木化學工業股份有限公司製造° POEM S-100 :甘油脂肪酸酯系辰 口又㈡曰乐界面活性劑,理研維生素 股份有限公司製造 μ 大豆卵磷脂:Tsuji-seiyu股份有限公司製造 (實施例3)還原型輔酶Q10對於健康人之精神狀況之改 善效果 利用雙盲試驗法來評價還原型輔酶Q10對精神狀況之改 善效果。將健康人36名(男性18名、女性18名)分成三群,每 天攝取3粒膠囊之表4記載之安慰劑膠囊或者還原型輔酶 Q10膠囊(其中,安慰劑群:安慰劑膠囊3粒,1〇〇mg攝取群: 安慰劑膠囊1粒+還原型辅酶q1〇膠囊2粒,3〇〇mg攝取群·· 還原型輔酶Q1 0勝囊3粒),進行4週,於攝取前後實施自覺 症狀之問卷調查。問卷調查中,讓參加者對各項目進行評 分,〇 ··完全無,1 ··幾乎沒有,2 :較少,3 :中等程度,4 ·· 高度’對於攝取前評分為2以上之則項目評價攝取後之改善 126845.doc •27- 200838496 率。其結果中,於易怒、無意慾、憂鬱、緊張感之4項目中 發現有用量依賴性之改善,因而表明藉由攝取還原型輔酶 Q10而改善該等精神狀況。 [表4] 試驗食組成表(每1粒4-圓形軟膠囊) 成分組成 還原型輔酶 Q10膠囊 安慰劑膠囊 氧化型輔酶Q1 〇(mg) 100 - (包含1重量%氧化型輔酶Q10) 紅花油(mg) 134.67 234.67 蜂蠟(mg) 4.33 4.33 POEM S-lOO(mg) 0.6 0.6 大立卵填脂(mg) 0.4 0.4 所使用之成分與實施例2相同 [表5] 還原型輔酶Q10之精神狀況改善效果 項目 改善率(%) 安慰劑 100 mg 300 mg 易怒 0 33 80 無意慾 0 33 75 憂鬱 0 85 100 緊張感 0 100 100 再者,改善率(%),係於各項目中膠囊攝取前評分為2以 上之對象者(期待改善該精神狀況之對象者)中,膠囊攝取後 評分較攝取前下降之對象者之比例。 (製劑例1)(散劑) 將氧化型輔酶Q1 〇溶解於丙醇中,繼而使其吸附於微晶纖 126845.doc -28- 200838496Safflower oil: manufactured by Nisshin-omio Co., Ltd., manufactured by Bees Butterfly, Ermu Chemical Industry Co., Ltd. ° POEM S-100: glycerol fatty acid ester, Chenkou (2) Yule interface active agent, made by Riken Vitamin Co., Ltd. Phospholipid: manufactured by Tsuji-seiyu Co., Ltd. (Example 3) Effect of reducing coenzyme Q10 on mental state of healthy person The double-blind test method was used to evaluate the effect of reduced coenzyme Q10 on mental state. 36 healthy people (18 males and 18 females) were divided into three groups, and three capsules of placebo capsules or reduced coenzyme Q10 capsules as shown in Table 4 (wherein, placebo group: 3 placebo capsules) were taken. 1 〇〇mg ingestion group: 1 capsule of placebo capsule + 2 capsules of reduced coenzyme q1 〇 capsule, 3 〇〇mg of ingestion group · · Reduced coenzyme Q1 0 capsules, 3 capsules), for 4 weeks, consciously before and after ingestion Questionnaire survey of symptoms. In the questionnaire survey, participants were asked to rate each item, 〇··completely absent, 1··almost no, 2: less, 3: moderate, 4 ··height' for projects with a score of 2 or higher before ingestion Evaluation of the improvement after ingestion 126845.doc •27- 200838496 rate. As a result, a dose-dependent improvement was found in the 4 items of irritability, unintentionality, depression, and nervousness, thus indicating that these mental states were improved by ingesting reduced coenzyme Q10. [Table 4] Test food composition table (each one 4-round soft capsule) Ingredients consisting of reduced coenzyme Q10 capsule placebo capsule oxidized coenzyme Q1 〇 (mg) 100 - (containing 1% by weight of oxidized coenzyme Q10) safflower Oil (mg) 134.67 234.67 Beeswax (mg) 4.33 4.33 POEM S-lOO (mg) 0.6 0.6 Da Li egg fat filling (mg) 0.4 0.4 The ingredients used are the same as in Example 2 [Table 5] The spirit of reduced coenzyme Q10 Condition improvement effect improvement rate (%) Placebo 100 mg 300 mg Irritability 0 33 80 Unintentional 0 33 75 Melancholy 0 85 100 Tension 0 100 100 Again, improvement rate (%), is the capsule intake in each item Among the subjects whose pre-scores are 2 or more (who are expected to improve the mental state), the ratio of the score after capsule intake is lower than that of the target before the ingestion. (Formulation Example 1) (Powder) The oxidized coenzyme Q1 is dissolved in propanol and then adsorbed to the microcrystalline fiber 126845.doc -28- 200838496
維素中,然後於減壓下加 殺粉混合,製成散劑。 氧化型辅酶Q 1 〇 微晶纖維素 玉米激粉 (製劑例2)(膠囊劑) M乾燥°將其於氮氣流中 10重量份 40重量份 55重量份 與玉米 田A 4 卜遮處方製作散劑, 用令法填充於明膠膠囊中。將έ >芦k 將、、工填充之膠囊密封後 兄中進行包裝,冷藏保存。 灸 氧化型辅酶Q10 微晶纖維素 玉米澱粉 乳糖 硬脂酸鎂 聚乙稀吡略烷酮 (製劑例3)(軟膠囊劑) 20重量份 40重量份 20重量份 65重量份 3重量份 2重量份 於氮 將玉米油加溫至50。(:,添加於相同溫度下熔融之氧化輔 酶Q10使其溶解。利用常法將其製成軟膠囊。 氧化型輔酶Q10 50重量份 3 5 0重量份 玉米油 (製劑例4)(錠劑) 將氧化型輔酶Q10溶解於丙醇中,使其吸附於微晶纖維素 中,然後於減壓下加以乾燥。於氮氣環境中將玉米澱粉、 乳糖、羧甲基纖維素鈣、硬脂酸鎂混合於其中,繼而添加 I26845.doc -29- 200838496 聚乙烯吡咯烷酮的水溶液作為黏合劑,利用常法將其製成 顆粒。於其中添加滑石粉作為潤滑劑再加以混合,然後打 20重量份 25重量份 15重量份 1 〇重量份 40重量份 5重量份 3重量份 1〇重量份 錠成錠劑。將錠劑於氮氣環境中進行包裝,冷藏保存。 氧化型辅酶Q 1 〇 玉米澱粉 乳糖 幾甲基纖維素舞 微晶纖維素 聚乙歸σ比咯烧酮 硬脂酸鎂 滑石粉 (製劑例5)(散劑) 還原型輔酶Q10 氧化型輔酶Q10 微晶纖維素 玉米澱粉 (製劑例6)(膠囊劑) 以與製劑例1同樣之方式,以下述處太制a r途處方製作散劑,然後利 用常法填充於明膠膠囊中。將經填充 昇元之膠囊密封後,於氮 氣環境中進行包裝,冷藏保存。 還原型輔酶Q10 19·6重量份 將還原型輔酶QH)(其中,包含2%之氧化型辅酶Qi〇)溶解 於丙醇中,繼而使其吸附於微晶纖維素中,然後於減壓下 加以乾燥。將其於氮氣流中與玉米澱粉混合,製成散劑。 9_8重量份 0.2重量份 4〇重量份 55重量份 126845.doc -30· 200838496 (K4重量份 40重量份 20重量份 65重量份 3重量份 2重量份 氧化型辅酶Q1 0 微晶纖維素 玉米澱粉 乳糖 硬脂酸儀 聚乙稀°比哈烧酉同 (製劑例7)(軟膠囊劑)In the vitamins, the powder is mixed with the powder under reduced pressure to prepare a powder. Oxidized Coenzyme Q 1 〇 Microcrystalline Cellulose Corn Powder (Formulation Example 2) (Capsule) M Dry ° 10 parts by weight of 40 parts by weight of 55 parts by weight in a nitrogen stream and a cornfield A 4 , filled in gelatin capsules with a method. Put the έ > 芦 k, and the filled capsules, seal them, and store them in cold storage. Moxibustion-oxidized Coenzyme Q10 Microcrystalline Cellulose Corn Starch Lactose Magnesium Stearate Polyvinylpyrrolidone (Formulation Example 3) (Soft Capsule) 20 parts by weight 40 parts by weight 20 parts by weight 65 parts by weight 3 parts by weight 2 weight The corn oil is warmed to 50 by nitrogen. (:, dissolved in oxidized coenzyme Q10 melted at the same temperature to dissolve it. It is made into a soft capsule by a conventional method. Oxidized Coenzyme Q10 50 parts by weight of 350 parts by weight of corn oil (Formulation Example 4) (tablet) The oxidized coenzyme Q10 is dissolved in propanol, adsorbed in microcrystalline cellulose, and then dried under reduced pressure. Corn starch, lactose, carboxymethylcellulose calcium, magnesium stearate in a nitrogen atmosphere Mixing with it, and then adding an aqueous solution of I26845.doc -29- 200838496 polyvinylpyrrolidone as a binder, which is granulated by a conventional method, and talc powder is added as a lubricant and then mixed, and then 20 parts by weight and 25 parts by weight are added. 15 parts by weight of 1 part by weight, 40 parts by weight, 5 parts by weight, 3 parts by weight, and 1 part by weight of the tablet. The tablet is packaged in a nitrogen atmosphere and stored in a refrigerated state. Oxidized Coenzyme Q 1 〇 Corn Starch Lactose Cellulose dance microcrystalline cellulose polyethyl sigma-pyrrolidone magnesium stearate talc powder (Formulation Example 5) (Powder) Reduced Coenzyme Q10 Oxidation Coenzyme Q10 Microcrystalline Cellulose Corn Starch (Formulation Example 6) capsule In the same manner as in Formulation Example 1, the powder was prepared in the following manner, and then filled in a gelatin capsule by a conventional method. The capsule filled with Shengyuan was sealed, packaged in a nitrogen atmosphere, and stored in a refrigerated manner. Reduced coenzyme Q10 19.6 parts by weight Reduced coenzyme QH) (including 2% oxidized coenzyme Qi 〇) was dissolved in propanol, which was then adsorbed to microcrystalline cellulose, and then decompressed Dry it underneath. It was mixed with corn starch in a stream of nitrogen to prepare a powder. 9_8 parts by weight 0.2 parts by weight 4 parts by weight 55 parts by weight 126845.doc -30· 200838496 (K4 parts by weight 40 parts by weight 20 parts by weight 65 parts by weight 3 parts by weight 2 parts by weight of oxidized coenzyme Q1 0 microcrystalline cellulose corn starch Lactose stearic acid meter, polyethylene, °, haha, and the same (formulation example 7) (soft capsule)
將玉米油加溫至50。(:,添加於相同溫度下熔融之還原型 輔酶Q10(其中,包含2%之氧化型輔酶q10)使其溶解。利用 常法將其製成軟膠囊。 還原型輔酶Q10 49重量份 氣化型辅酶Q10 1重量份 玉米油 350重量份 (製劑例8)(錠劑) 將還原型輔酶Q10(其中,包含2%之氧化型辅酶q1〇)溶解 於丙醇中,使其吸附於微晶纖維素中,然後於減壓下加以 乾知。於氮氣環境中將玉米澱粉、乳糖、羧甲基纖維素鈣、 更知馱鎂混合於其中,繼而添加聚乙烯吡咯烷酮的水溶液 :=黏合劑,利用常法將其製成顆粒。添加滑石粉作為潤 ’月4再加以混合,然後打錠成錠劑。將錠劑於氮氣環境中 進行包裝,冷藏保存。 還原型輔酶Q10 19.6重量份 氧化型辅酶Q10 0.4重量份 玉米殺粉 μ壬〇 126845.doc 31- 200838496 乳糖 1 5重量份 羧甲基纖維素約 1〇重量伤^ 微晶纖維素 4 〇重量份 聚乙烯吡咯烷酮 5重量份 硬脂酸鎂 3重量份 滑石粉 10重量份 (製劑例9)(膠囊劑)Warm the corn oil to 50. (:, the reduced coenzyme Q10 (containing 2% of the oxidized coenzyme q10) which was melted at the same temperature was dissolved and dissolved in a soft capsule by a conventional method. Reduced coenzyme Q10 49 parts by weight gasification type Coenzyme Q10 1 part by weight of corn oil 350 parts by weight (Formulation Example 8) (tablet) The reduced coenzyme Q10 (containing 2% of the oxidized coenzyme q1 oxime) is dissolved in propanol to be adsorbed to the microcrystalline fiber The medium is then dried under reduced pressure. Corn starch, lactose, calcium carboxymethylcellulose, and more magnesium strontium are mixed in a nitrogen atmosphere, followed by an aqueous solution of polyvinylpyrrolidone: = binder, utilized It is made into granules by the usual method. The talc powder is added as the wetting 'month 4 and then mixed, and then the tablet is put into a tablet. The tablet is packaged in a nitrogen atmosphere and stored in a refrigerated state. Reduced coenzyme Q10 19.6 parts by weight of oxidized coenzyme Q10 0.4 parts by weight corn powder 壬〇 壬〇 壬〇 126845.doc 31- 200838496 lactose 15 parts by weight carboxymethyl cellulose about 1 〇 weight injury ^ microcrystalline cellulose 4 〇 parts by weight polyvinylpyrrolidone 5 parts by weight magnesium stearate 3 parts by weight slippery 10 parts by weight of stone powder (Formulation Example 9) (capsule)
以與製劑例1同樣之方式,以下沭余+…… 卜建處方製作散劑, 用常法填充於明膠膠囊中。將锃 严 、工填充之膠囊密封後 氣環境中進行包裝,冷藏保存。 然後利 ,於氮In the same manner as in Formulation Example 1, the following formulas were prepared: ... Bu Jian prescription to prepare a powder, which was filled in a gelatin capsule by a usual method. The sealed and filled capsules are sealed and stored in an air environment. Then benefit, nitrogen
氧化型輔酶Q1 〇 維生素B 維生素C 維生素E 微晶纖維素 玉米澱粉 乳糖 硬脂酸鎂 聚乙烯咣咯烷酮 (製劑例10)(膠囊劑) 20重量份 20重量份 40重量份 20重量份 40重量份 20重量份 65重量份 3重量份 2重量份 ”取叫椚丄同樣之方式,以用常法填充於明膠膠囊 述處”氣環境中進行包裝,冷藏保存,填充之耀還原型辅酶Q1〇 20重量份 然後利 ,於氮 126845.doc -32- 200838496 1重量份 20重量份 40重量份 20重量份 40重量份 2 0重量份 65重量份 3重量份 2重量份 氧化型輔酶Q10 維生素B 維生素C 維生素E 微晶纖維素 玉米澱粉 乳糖Oxidized Coenzyme Q1 〇 Vitamin B Vitamin C Vitamin E Microcrystalline Cellulose Corn Starch Lactose Magnesium Stearate Polyvinylpyrrolidone (Formulation Example 10) (Capsule) 20 parts by weight 20 parts by weight 40 parts by weight 20 parts by weight 40 20 parts by weight, 6 parts by weight, 6 parts by weight, 3 parts by weight, 2 parts by weight, "in the same manner, filled in a gelatin capsule in a conventional manner", packaged in an air environment, stored in a refrigerated state, and filled with a reduced coenzyme Q1 〇 20 parts by weight and then benefit, nitrogen 126845.doc -32- 200838496 1 part by weight 20 parts by weight 40 parts by weight 20 parts by weight 40 parts by weight 20 parts by weight 65 parts by weight 3 parts by weight 2 parts by weight oxidized coenzyme Q10 vitamin B Vitamin C Vitamin E Microcrystalline Cellulose Corn Starch Lactose
硬脂酸鎂 聚乙浠ϋ比略烧酮Magnesium stearate
(製劑例11)(膠囊劑) 以與製劑例1同樣之方式, 、Μ下迷處方製作散劑 用常法填充於明膠膠囊中。 .^ Α 肘、、工填充之膠囊密封 ㈣境中進行包裝,進行冷藏保存。 然後利 ,於氮 氧化型輔酶Q1 〇 麩胱甘肽 微晶纖維素 玉米澱粉 乳糖 硬脂酸鎂 聚乙浠吡咯烷酮 (製劑例12) 20重量份 20重量份 40重量份 20重量份 65重量份 3重量份 2重量份 (膠囊劑) 以與製劑例!同樣之方式 , 用常法填充於明膠膠囊 壤:方製作散 氣環境中進行包裝,冷藏保Γ充之膠囊密 126845.doc 然後利 ,於氮 -33- 200838496 還原型輔酶Q10 20重量份 氧化型輔酶Q10 1重量份 麩胱甘肽 20重量份 微晶纖維素 40重量份 玉米澱粉 20重量份 乳糖 65重量份 硬脂酸鎂 3重量份 聚乙烯吼洛烧酉同 2重量份(Formulation Example 11) (Capsule) In the same manner as in Formulation Example 1, the powder was prepared by filling the gelatin capsule in a usual manner. .^ Α Elbow, and the filled capsule seal (4) Packed in the environment for cold storage. Then, in the nitrogen oxidation type coenzyme Q1 glutathione microcrystalline cellulose corn starch lactose magnesium stearate polyvinylpyrrolidone (Formulation Example 12) 20 parts by weight 20 parts by weight 40 parts by weight 20 parts by weight 65 parts by weight 3 2 parts by weight (capsule) in parts by weight and preparation examples! In the same way, it is filled in the gelatin capsule soil by the usual method: the package is made in a diffused atmosphere for packaging, and the capsule is 1200845.doc, and then the nitrogen-33-200838496 reduced coenzyme Q10 20 parts by weight oxidation type. Coenzyme Q10 1 part by weight glutathione 20 parts by weight microcrystalline cellulose 40 parts by weight corn starch 20 parts by weight lactose 65 parts by weight magnesium stearate 3 parts by weight polyethylene strontium bismuth with 2 parts by weight
(製劑例13)(散劑) ,繼而使其吸附 於氮氣流中將 將氧化型辅酶Q10與芝麻素溶解於丙醇中 於微晶纖維素中,然後於減壓下加以乾燥 其與玉米澱粉混合,製成散劑。 氧化型輔酶Q10 10重量份 芝麻素 10重量份 微晶纖維素 40重量份 玉米殿粉 5 5重量份 (製劑例14)(散劑) 將還原型辅酶Q10(其中,包含2%之氧化型輔酶q10)與芝 麻素溶解於丙醇中,繼而使其吸附於微晶纖維素中,然後 於減壓下加以乾燥。於氮氣流中將其與玉米澱粉混合,製 成散劑。 9.8重量份 0.2重量份 10重量份 還原型辅酶Q10 氧化型輔酶Q10 芝麻素 126845.doc 34- 200838496 微晶纖維素 40重量份 玉朱ί殿粉 5 5重量份 (製劑例15)(軟膠囊劑) 將玉米油加溫至50°C,加入於相同溫度下熔融的氧化辅 酶Q10及甘草萃取物使其溶解。利用常法將其製成軟膠囊。 氧化型輔酶Q10 50重量份 甘草萃取物 25重量份(Formulation Example 13) (volume), which is then adsorbed in a nitrogen stream, and the oxidized coenzyme Q10 and sesamin are dissolved in propanol in microcrystalline cellulose, and then dried under reduced pressure to be mixed with corn starch. , made into powder. Oxidized Coenzyme Q10 10 parts by weight Sesamin 10 parts by weight Microcrystalline cellulose 40 parts by weight Corn cake powder 5 5 parts by weight (Formulation Example 14) (Powder) Reduced Coenzyme Q10 (including 2% oxidized coenzyme q10) Sesamin is dissolved in propanol, which is then adsorbed to microcrystalline cellulose, and then dried under reduced pressure. It was mixed with corn starch in a stream of nitrogen to prepare a powder. 9.8 parts by weight, 0.2 parts by weight, 10 parts by weight, reduced coenzyme Q10, oxidized coenzyme Q10, sesamin 126845.doc 34-200838496 microcrystalline cellulose, 40 parts by weight, Yuzhu yudian powder, 5 parts by weight (formulation 15) (soft capsule) The corn oil was warmed to 50 ° C, and oxidized coenzyme Q10 and licorice extract melted at the same temperature were added to dissolve. It is made into a soft capsule by a conventional method. Oxidized Coenzyme Q10 50 parts by weight Licorice Extract 25 parts by weight
玉米油 325重量份 (製劑例16)(軟膠囊劑) 將玉米油加溫至5〇°C,加入於相同溫度下熔融的還原型 輔酶Q10(其中,包含2%之氧化型輔酶q1〇)及甘草萃取物使 其溶解。利用常法將其製成軟膠囊。 還原型輔酶Q10 49重量份 氧化型輔酶Q10 1重量份 甘草萃取物 25重量份 玉米油 325重量份 以上,詳細說明了本發明之幾個具體態樣,業者對於所 揭不之特定悲樣’可在不實質脫離本發明之教示及優點之 fe圍内進行各種修正及變更。因此,如此修正及變更亦包 έ於所有下述申請專利範圍中被請求之本發明之精神及範 圍内。 本申请案係以於日本國經申請之日本專利特願 2006-31 1670為基礎,其内容全部包含於本說明書中。 126845.doc -35-325 parts by weight of corn oil (Formulation Example 16) (soft capsule) The corn oil was warmed to 5 ° C, and reduced coenzyme Q10 (containing 2% of the oxidized coenzyme q1 熔融) which was melted at the same temperature was added. And the licorice extract is dissolved. It is made into a soft capsule by a conventional method. Reduced coenzyme Q10 49 parts by weight oxidized coenzyme Q10 1 part by weight licorice extract 25 parts by weight corn oil 325 parts by weight or more, detailing several specific aspects of the invention, the industry can not reveal the specific sadness Various modifications and changes can be made without departing from the spirit and scope of the invention. Therefore, such modifications and variations are intended to be included within the spirit and scope of the invention as claimed. The present application is based on Japanese Patent Application No. 2006-31 1670, the entire disclosure of which is incorporated herein by reference. 126845.doc -35-
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CN101658233B (en) * | 2009-09-07 | 2011-10-05 | 汕头市新特医药有限公司 | A kind of compressed candy and its manufacturing method |
US8828453B2 (en) * | 2010-04-29 | 2014-09-09 | Betul Hatipoglu | Herbal-based compositions for alleviating symptoms associated with autism |
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